During the tenure of a K04, I intend to pursue the following specific questions: 1. Analyze the molecular biology of normal, mutant, and retinoic-acid-induced cell death in the interdigital region of the developing mouse by examination of light- and electron microscopic morphology, DNA fragmentation; RNA and protein synthesis, and expression of genes associated with cell death such as transglutaminase, TRPM-2 and Bcl-2). 2) Establish an in vitro organ culture system as a model for studying limb development and cell death. II. Isolate genes related to programmed cell death: A. Establishment of stage-specific cDNA libraries for isolation of developmental stage specific and cell death related genes. B. Isolate and characterize common cDNAs activated during involution of Manduca labial gland and muscle.